Single-cell RNA-sequencing (scRNA-Seq) is widely used to reveal the heterogeneity and dynamics of tissues, organisms, and complex diseases, but its analyses still suffer from multiple grand challenges, including the sequencing sparsity and complex differential patterns in gene expression. We introduce the scGNN (single-cell graph neural network) to provide a hypothesis-free deep learning framework for scRNA-Seq analyses. This framework formulates and aggregates cell–cell relationships with graph neural networks and models heterogeneous gene expression patterns using a left-truncated mixture Gaussian model. scGNN integrates three iterative multi-modal autoencoders and outperforms existing tools for gene imputation and cell clustering on four benchmark scRNA-Seq datasets. In an Alzheimer’s disease study with 13,214 single nuclei from postmortem brain tissues, scGNN successfully illustrated disease-related neural development and the differential mechanism. scGNN provides an effective representation of gene expression and cell–cell relationships. It is also a powerful framework that can be applied to general scRNA-Seq analyses.

Circular RNAs (circRNAs) are a unique class of RNA molecule identified more than 40 years ago which are produced by a covalent linkage via back-splicing of linear RNA. Recent advances in sequencing technologies and bioinformatics tools have led directly to an ever-expanding field of types and biological functions of circRNAs. In parallel with technological developments, practical applications of circRNAs have arisen including their utilization as biomarkers of human disease. Currently, circRNA-associated bioinformatics tools can support projects including circRNA annotation, circRNA identification and network analysis of competing endogenous RNA (ceRNA). In this review, we collected about 100 circRNA-associated bioinformatics tools and summarized their current attributes and capabilities. We also performed network analysis and text mining on circRNA tool publications in order to reveal trends in their ongoing development.

BackgroundThe Internet has become one of the most important means to obtain health and medical information. It is often the first step in checking for basic information about a disease and its treatment. The search results are often useful to general users. Various search engines such as Google, Yahoo!, Bing, and Ask.com can play an important role in obtaining medical information for both medical professionals and lay people. However, the usability and effectiveness of various search engines for medical information have not been comprehensively compared and evaluated.ObjectiveTo compare major Internet search engines in their usability of obtaining medical and health information.MethodsWe applied usability testing as a software engineering technique and a standard industry practice to compare the four major search engines (Google, Yahoo!, Bing, and Ask.com) in obtaining health and medical information. For this purpose, we searched the keyword breast cancer in Google, Yahoo!, Bing, and Ask.com and saved the results of the top 200 links from each search engine. We combined nonredundant links from the four search engines and gave them to volunteer users in an alphabetical order. The volunteer users evaluated the websites and scored each website from 0 to 10 (lowest to highest) based on the usefulness of the content relevant to breast cancer. A medical expert identified six well-known websites related to breast cancer in advance as standards. We also used five keywords associated with breast cancer defined in the latest release of Systematized Nomenclature of Medicine-Clinical Terms (SNOMED CT) and analyzed their occurrence in the websites.ResultsEach search engine provided rich information related to breast cancer in the search results. All six standard websites were among the top 30 in search results of all four search engines. Google had the best search validity (in terms of whether a website could be opened), followed by Bing, Ask.com, and Yahoo!. The search results highly overlapped between the search engines, and the overlap between any two search engines was about half or more. On the other hand, each search engine emphasized various types of content differently. In terms of user satisfaction analysis, volunteer users scored Bing the highest for its usefulness, followed by Yahoo!, Google, and Ask.com.ConclusionsGoogle, Yahoo!, Bing, and Ask.com are by and large effective search engines for helping lay users get health and medical information. Nevertheless, the current ranking methods have some pitfalls and there is room for improvement to help users get more accurate and useful information. We suggest that search engine users explore multiple search engines to search different types of health information and medical knowledge for their own needs and get a professional consultation if necessary.

We have developed a generally adaptable, novel high-throughput Viral Chromosome Conformation Capture assay (V3C-seq) for use in trans that allows genome-wide identification of the direct interactions of a lytic virus genome with distinct regions of the cellular chromosome. Upon infection, we found that the parvovirus Minute Virus of Mice (MVM) genome initially associated with sites of cellular DNA damage that in mock-infected cells also exhibited DNA damage as cells progressed through S-phase. As infection proceeded, new DNA damage sites were induced, and virus subsequently also associated with these. Sites of association identified biochemically were confirmed microscopically and MVM could be targeted specifically to artificially induced sites of DNA damage. Thus, MVM established replication at cellular DNA damage sites, which provide replication and expression machinery, and as cellular DNA damage accrued, virus spread additionally to newly damaged sites to amplify infection. MVM-associated sites overlap significantly with previously identified topologically-associated domains (TADs).

Genomic selection uses single-nucleotide polymorphisms (SNPs) to predict quantitative phenotypes for enhancing traits in breeding populations and has been widely used to increase breeding efficiency for plants and animals. Existing statistical methods rely on a prior distribution assumption of imputed genotype effects, which may not fit experimental datasets. Emerging deep learning technology could serve as a powerful machine learning tool to predict quantitative phenotypes without imputation and also to discover potential associated genotype markers efficiently. We propose a deep-learning framework using convolutional neural networks (CNNs) to predict the quantitative traits from SNPs and also to investigate genotype contributions to the trait using saliency maps. The missing values of SNPs are treated as a new genotype for the input of the deep learning model. We tested our framework on both simulation data and experimental datasets of soybean. The results show that the deep learning model can bypass the imputation of missing values and achieve more accurate results for predicting quantitative phenotypes than currently available other well-known statistical methods. It can also effectively and efficiently identify significant markers of SNPs and SNP combinations associated in genome-wide association study.